Monitoring disposition of tethered capsule endoscope in esophagus

ABSTRACT

A system for imaging a body lumen includes a scanning capsule with a scanning device, a flexible tether coupled to the scanning capsule, a reel coupled to the flexible tether, and one or more processors. The scanning capsule is sized to be introduced into the body lumen of the patient by swallowing and advanced along the body lumen with normal peristalsis. The one or more processors are configured to scan light onto a portion of the body lumen using the scanning device, detect light from the portion of the body lumen using a light sensor, generate one or more images of the portion of the body lumen in response to the detected light, determine a rate for withdrawing the scanning capsule from the body lumen based on the one or more images, and withdraw the scanning capsule from the body lumen using the reel according to the determined rate.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.11/852,227, filed Sep. 7, 2007, now U.S. Pat. No. 9,161,684, which is acontinuation-in-part (CIP) of U.S. patent application Ser. No.11/069,826, filed on Feb. 28, 2005, now U.S. Pat. No. 7,530,948, thedisclosures of which are incorporated herein by reference in theirentirety.

BACKGROUND

Barrett's Esophagus (BE) is a condition of the esophagus that ispre-cancerous, a precursor to cancer of the esophagus. The standardpractice for diagnosing Barrett's Esophagus uses a flexible endoscopyprocedure, often with the esophageal lumen insufflated with air. Anormal esophagus is usually light pink in color, while the stomachappears slightly darker pink. Barrett's Esophagus usually manifestsitself as regions of slightly darker pink color above the loweresophageal sphincter (LES) that separates the stomach from theesophagus.

It is preferable to diagnose BE early, since this condition has beenfound to be a precursor of esophageal adenocarcinoma. Accordingly, itwould be desirable to provide a general screening procedure for thecondition, even though doing so would require evaluating the conditionof the esophagus in millions of people with chronic heartburn andgastric reflux. However, Barrett's Esophagus and early stage cancers canoccur without telltale symptoms, so mass screenings have been proposedas the only viable approach to identify the condition as early aspossible to enable treatment and avoid the onset of or provide acurative therapy for the cancerous condition. Unfortunately, the numbersof people that are likely candidates for esophageal screening and thecurrent cost associated with the practice of flexible endoscopyperformed by a physician compared to the reimbursement associated withsuch mass screenings make this solution currently impractical because ofthe expense involved.

What is needed is a much more efficient and cost effective approach foridentifying those people having Barrett's Esophagus. Only a doctor canperform an examination of the esophagus using a conventional flexibleendoscope, and the procedure is thus relatively expensive. It would bepreferable to develop a different scanning technique that need not beperformed by a physician, but instead, can be performed by a trainedmedical technician or nurse. Indeed, it would also be desirable toautomate the evaluation of images produced by imaging the internalsurface of the esophagus just proximal of the LES so that the existenceof Barrett's Esophagus can be automatically detected either in real timeduring the scanning operation or immediately thereafter.

To facilitate mass screenings of individuals who may be afflicted withBarrett's Esophagus, it would be desirable to employ a screening devicethat can readily be introduced into the esophagus, without invoking anygag reflex. Ideally, the scanning device should be embodied in acapsule-shaped housing so that it can simply be swallowed with a glassof water. Accordingly, the device must be sufficiently small in size toenable it to be swallowed by most patients. Further, although such adevice might be reusable if properly sterilized, it may be desirable toemploy a screening device that is sufficiently low in cost as to bedisposable after a single use.

The above-noted earlier related application discloses an approach formonitoring a position in a person's esophagus of an endoscope that iswell-suited for providing images that can be used to evaluate thecondition of the esophagus and thereby detect BE. In this earlierapproach, a tether attached to a capsule endoscope that includes animaging device passes over a wheel that rotates as the capsule is movedaxially within the esophagus, to enable the relative position of thecapsule in the esophagus to be continually monitored. The axial positionof the capsule is important so that the locations of regions, which maybe of interest in images of the inner surface of the esophagus, can beidentified and to enable the axial scaling of any panoramic imagestaken. However, the measurement of the axial position depends upon thefrictional contact between the tether and the measurement wheel. Thereare three reasons why this method may not produce sufficiently accurateresults. In this earlier described approach, the tether must be keptunder tension, and the measurement technique relies on no-slip frictionbetween the measurement wheel and the moving tether. Slippery saliva andmucus within the person's mouth and esophagus can adhere to the tethercreating slippage between the measurement wheel that is rotated and thetether. In addition, the clinician performing the procedure may want tofeel the progression of the tethered capsule scope as it passes throughthe lower esophageal sphincter and other parts of the esophagus, and theadditional applied tension produced by the measurement wheel (which wasdisclosed as a pinch wheel) is likely to interfere with that feel.Similarly, the clinician may want to move the capsule scope up and downwithin the esophagus in a repeated manner, which will likely introducemeasurement error in a mechanical system that is based on the frictionbetween the measurement wheel and the tether. Any hysteresis in themeasurement can be a further source of error.

Accordingly, a better technique for monitoring the axial position of thecapsule scope is desired. The approach that is used should monitor themovement of the capsule by detecting the motion of the tether withoutactual contact between the tether and the axial position monitoringapparatus. The presence of saliva and mucus should have minimal impacton the monitoring technique used, and the feel as the capsule scope ismoved up and down should be readily experienced by the clinician withoutinterference from the apparatus used to monitor the position of thecapsule.

SUMMARY

A scanning fiber endoscope (SFE) includes a scanning capsule having ascanning device and a tether coupled to the capsule for controlling aposition of the scanning capsule within a body lumen. Since it isimportant to monitor at least a relative position of the scanningcapsule without introducing errors as a result of bodily fluids that maycoat the tether and to avoid interfering with the “feel” of a clinicianwho is controlling the position of the scanning capsule within the bodylumen, a novel method has been developed to achieve this function. Themethod thus enables monitoring a relative position of a scanning capsulewithin a body lumen. The tether that has a distal end coupled to thecapsule extends externally of the body lumen and carries a scan signalproduced in the scanning capsule that is useful to produce an image ofan interior surface of the body lumen. The method includes the step ofproviding an indicia along an axial length of at least a portion of thetether, which is indicative of a position. Using a sensor that respondsto the indicia without requiring physical contact with the tether, theindicia are automatically sensed, producing a position signal indicativeof the position of the tether and thus, of the disposition of thescanning capsule axially within the body lumen.

At least one non-numeric visible reference mark can be provided on thetether to indicate an expected reference position. This reference markcan thus enable a user to manually position the capsule at about adesired location based upon the visual indication provided by thenon-numeric visible reference mark on the tether. While not arequirement, the body lumen can comprise an esophagus. In this case, theexpected reference position might correspond to a position on the tetherthat should indicate when the capsule is expected to be disposed atabout a gastroesophageal junction in the esophagus. A plurality ofadditional non-numeric visible marks can also be provided both distallyand proximally of the at least one non-numeric visible reference mark,to visually indicate positions or distances on either side of theexpected reference position.

In one exemplary embodiment, the step of automatically sensing theindicia can include the step of using a magnetic sensor for producingthe position signal in response to a varying parameter of a magneticfield that is produced by the indicia on the tether. The position signalthat is produced can be either a digital position signal or an analogposition signal, both of which are indicative of a current positionalong the axial length of the tether, adjacent to the magnetic sensor.

In a different exemplary embodiment, an optical sensor can be used forproducing the position signal in response to an optical parameter of theindicia that varies along the axial length of the tether. Again, thestep of producing the position signal can produce either a digitalposition signal or an analog position signal, either of which isindicative of a current position along the axial length of the tether,adjacent to the optical sensor. The indicia can comprise an optical codethat produces the position signal in response to at least one parameterselected from a group of parameters. These parameters include: a colorof the optical code that is sensed by the optical sensor; a digitalvalue indicated by the optical code; an intensity of light reflectedfrom the optical code compared to an intensity of light reflected from abackground area; a pattern of the optical code that conveys digitalinformation; a relative size of markings comprising the optical code; ashape of the markings comprising the optical code; a scattering of lightby the optical code compared to a scattering of light from thebackground area; and a wavelength of light reflected by or absorbed bythe optical code.

In a further alternative exemplary embodiment, an additional sensor canbe provided to monitor the indicia on the tether, to increase aresolution with which the relative position of the capsule in the bodylumen is determined.

The step of providing the indicia can include applying the indicia byeither affixing the indicia to the tether as a longitudinally extendingtape, or by applying the indicia to the tether as a longitudinallyextending coating. Optionally, the indicia can be protected with aprotective coating that is applied over the indicia. In some exemplaryembodiments, the method can include the step of providing a scraper forgently wiping bodily fluids from the tether as the tether is withdrawnfrom the body lumen, and before the tether passes the position sensor.

In some applications, the exemplary method includes the step ofdetermining a reference position for the capsule within the body lumenrelative to which the indicia are used, to determine the position of thecapsule within the body lumen. For example, the reference position canbe determined by moving the capsule to a known position within the bodylumen based upon the images of an interior surface of the body lumen.The disposition of the capsule at the known position thus represents thereference position that is then used to determine subsequent positionsof the capsule as the tether is used to move the capsule within the bodylumen.

Another aspect of the present technology is directed to exemplaryapparatus for measuring a relative position in a body lumen of a capsuleused for scanning an inner surface of the body lumen to produce images.The apparatus includes a tether and a non-contact position sensor thatare generally consistent with the method discussed above.

Yet another aspect of this technology is directed to an exemplary methodfor measuring an axial extent of a region of interest within a bodylumen in regard to images produced by a scanning device in a capsulethat is coupled to a tether having a proximal end that extends outsidethe body lumen and is used to move the capsule. The method includes thestep of monitoring the distance that the capsule is moved through thebody lumen with the tether by monitoring movement of the tether past asensor disposed outside the body lumen. Successive images of an internalsurface of the body lumen are captured as the tether is used to move thecapsule axially through the body lumen. A region of interest on theinternal surface of the body lumen is detected in the successive images,and based upon a first position of the capsule within the body lumencorresponding to an axial start and a second position corresponding toan axial end of the region of interest, the axial extent of the regionof interest is measured, with reference to the distance between thefirst position and the second position that the tether moves thecapsule. Also disclosed below is an apparatus for carrying out thisdistance measuring function.

Still another aspect of the technology is directed to a method for usewith a capsule having a scanner for imaging an inner surface of anesophagus, where the capsule is coupled to a tether for moving thecapsule within the esophagus and through a gastroesophageal junction. Inthis method (and in regard to corresponding apparatus) using the tether,the capsule is moved within the esophagus to a position adjacent to thegastroesophageal junction. A pulse of pressurized fluid is thendelivered to a region adjacent to the capsule. The pulse of pressurizedfluid causes a lower portion of the esophagus to autonomously bedistended, thereby facilitating movement of the capsule through thegastroesophageal junction and into and out of a stomach of a patient,while a scanner in the capsule is used for imaging the inner surface ofthe esophagus.

This Summary has been provided to introduce a few concepts in asimplified form that are further described in detail below in theDescription. However, this Summary is not intended to identify key oressential features of the claimed subject matter, nor is it intended tobe used as an aid in determining the scope of the claimed subjectmatter.

DRAWINGS

Various aspects and attendant advantages of one or more exemplaryembodiments and modifications thereto will become more readilyappreciated as the same becomes better understood by reference to thefollowing detailed description, when taken in conjunction with theaccompanying drawings, wherein:

FIG. 1A is a schematic view showing an esophagus and stomach, toillustrate how one body lumen can be readily scanned using the presentinvention;

FIG. 1B is a schematic view of a portion of the esophagus and stomach ofFIG. 1A, showing how the present invention is controllably disposed toscan a desired portion of the esophagus to detect a BE condition;

FIG. 2 is an enlarged isometric view of one embodiment of the presentinvention and indicating the relative wide field of view (FOV) providedby the scanner used therein;

FIG. 3 is a block diagram illustrating the functional flow of signals ina scanning system in accord with the present invention, which is usablefor monitoring, rendering diagnoses, and providing therapy to an innersurface of a lumen in a patient's body;

FIG. 4 illustrates a scanner embodiment having an actuator for driving ascanning optical fiber with a microlens, for use as an optical beamscanner with a scan lens, in connection with the present invention;

FIG. 5 is a schematic view of a point-source imaging embodiment,illustrating the variations in the imaged spot diameter at differentscanning angles, in connection with a scanner used in the presentinvention;

FIG. 6A is a schematic view of a scanning point-source illuminator withtime-series photon detectors and imaging lenses for use in a scanner ofthe present invention;

FIG. 6B is a schematic view of a scanning optical beam illuminator witha scan lens and detectors, for use in a scanner of the presentinvention;

FIG. 6C is a schematic diagram showing a configuration for a scannerusing a bundle of optical fibers and a single concentric core opticalfiber;

FIGS. 6D and 6E schematically illustrate a scanner having distal photonred, green, blue (RGB) filtration and detection using stereo-pairedgeometry and the ability to subtract background scatter using forwardand side-facing spatial arrangements of detectors, respectively shown ina side elevational view and in an end view;

FIGS. 6F and 6G schematically illustrate a scanner having distal photonpolarized filtration and detection using stereo-paired geometry and theability to enhance signals from superficial tissue on the inner surfaceof a lumen, using forward and side-facing spatial arrangements ofdetectors, respectively shown in a side elevational view and in an endview;

FIG. 7A is a schematic diagram showing the configuration of a scannerwith distal optical fiber position sensors and proximally disposedphoton detectors with proximal optical fiber light collectors that arecapable of pseudo-stereo image acquisition;

FIG. 7B is a schematic diagram of an optical fiber scanning system foruse with the present invention, which employs radiation from visible andUV laser sources combined with dichroic filters;

FIG. 7C is a schematic diagram of an optical fiber system for use withthe present invention, which employs radiation from visible and IR lasersources combined with fiber optic combiners connected in series;

FIGS. 8A, 8B, and 8C respectively illustrate a top plan view, a sideelevational cross-sectional view taken along section line 8B-8B in FIG.8A, and an end view taken along section line 8C-8C in FIG. 8A, of anembodiment of a thin film, microelectromechanical (MEMS) system scannerthat is usable in the present invention;

FIG. 8D illustrates an end elevational view of another embodiment thatincludes a pair of thin film parallel cantilevers for illumination of aninterior surface of a lumen;

FIG. 9 illustrates a medical practitioner using the present invention tocarry out automated scanning and diagnostic evaluation of a patient'sesophagus, such as might occur during mass screenings of the generalpopulation for BE;

FIG. 10 is a block diagram illustrating the functional input and outputcomponents of an optical fiber scanner system for use with the presentinvention;

FIG. 11A is a functional block diagram of an integrated cancer imaging,screening, and biopsy system, with optical therapy delivery andmonitoring capabilities using a capsule and scanner in accord with thepresent invention;

FIG. 11B is a functional block diagram of an integrated cancer imagingand diagnostic system, with stereograph surgical support and displaycapabilities using a capsule and scanner in accord with the presentinvention;

FIG. 12 is a schematic side elevational view illustrating an exemplaryembodiment of a non-contact optical sensor that is used to measure aposition of a tether and thus, the position of a scanning capsule thatis coupled to the tether, within an esophagus of a patient, in responseto optical indicia provided on the tether;

FIG. 13 is a schematic side elevational view illustrating an exemplaryembodiment of a non-contact magnetic sensor that is used to measure aposition of a tether and a scanning capsule within an esophagus of apatient, in response to magnetic indicia provided on the tether;

FIG. 14 is an exemplary schematic block diagram illustrating how thetether and the non-contact sensor that monitors the disposition of acapsule are coupled to functional components of a scanning fiberendoscope (SFE) base station;

FIG. 15 is a schematic elevational view of a portion of a tether,showing how an exemplary elastomeric scraper is used to wipe saliva andmucous from the tether as the tether is pulled from the esophagus of apatient, past a non-contact sensor that measures the position of thetether and capsule within the esophagus;

FIG. 16 is a schematic view of a capsule having a balloon attached,wherein the balloon is shown inflated in a lumen;

FIG. 17 is a schematic view of a capsule having electrodes to causemuscle tissue peristalsis that advances the capsule through a lumen;

FIG. 18 is a schematic view of a capsule having a tether that includesan annular channel through which a biopsy instrument, such as acytological brush is advanced to take a biopsy of tissue from an innersurface of a lumen;

FIG. 19 is a schematic view of a capsule having a pyramidal-shapedmirror for simultaneously laterally imaging opposite inner surfaces of alumen, showing how the tether can be used to rotate the capsule asneeded to encompass a full view of the inner surface of a lumen;

FIG. 20A is a representation of an exemplary analog pattern applied to atether to enable a non-contact sensor to determine a position of thetether and the attached capsule within an esophagus, based upon theanalog signal produced, for example, by an optical sensor responding tothe analog pattern;

FIG. 20B is a representation of an exemplary digital pattern applied toa tether to enable a non-contact sensor to determine a position of thetether and the attached capsule within an esophagus, based upon thedigital signal produced, for example, by an optical sensor responding tothe digital pattern;

FIG. 21 is a schematic view of an exemplary embodiment that includesdual optical sensors with lenses, for responding to a dual color opticalpattern applied to a tether, to determine the relative position of thetether/capsule in a body lumen such as the esophagus;

FIG. 22A is a schematic cut away view of an exemplary tether with dataapplied on a data layer protected by a transparent coating;

FIG. 22B is a transverse cross-sectional view of the tether, data layer,and protective coating, taken along section line 22B of FIG. 22A;

FIG. 23 is an exemplary view of a tether provided with visible markingsthat indicate the expected portion of the tether that must be insertedinto an esophagus so that the capsule will be disposed at about thegastroesophageal junction where the esophagus is joined to the stomach;

FIG. 24 is a schematic illustration of an exemplary embodiment thatincludes a passage to convey a pulse of pressurized air (or other fluid)to a point proximal the capsule, to autonomously cause the esophagus todistend;

FIG. 25 is a schematic illustration of another exemplary embodiment thatincludes an adjacent external tube used to convey a pulse of pressurizedair (or other fluid) to a point proximal the capsule; and

FIG. 26 is a schematic illustration of still another exemplaryembodiment that an external tube that is slid over the tether and isused to convey a pulse of pressurized air (or other fluid) to a pointproximal the capsule.

DESCRIPTION Figures and Disclosed Embodiments are not Limiting

Exemplary embodiments are illustrated in referenced Figures of thedrawings. It is intended that the embodiments and Figures disclosedherein are to be considered illustrative rather than restrictive. Nolimitation on the scope of the technology and of the claims that followis to be imputed to the examples shown in the drawings and discussedherein.

Exemplary Application of Scanning Capsule

Although an exemplary embodiment of a scanning capsule was initiallyconceived as a solution for providing relatively low cost mass screeningof the general population to detect BE without requiring interaction bya physician, it will be apparent that this embodiment is also generallyapplicable for use in scanning, providing diagnoses, rendering therapy,and monitoring the status of therapy thus delivered to an inner surfaceof almost any lumen in a patient's body. Accordingly, although thefollowing discussion often emphasizes the application of the scanningcapsule in the detection of BE, it is not intended that the applicationof this device be in any way limited to that specific application.

FIG. 1A includes a schematic illustration 10 showing a stomach 12, anesophagus 14, and a lower esophageal sphincter (LES) 16. LES 16 normallyacts as a one-way valve, opening to enable food that is swallowed downthe esophagus 14 to pass freely into stomach 12, but normally preventingacid and food from moving back up into the esophagus 14 from insidestomach 12. However, as noted above in the Background of the Invention,people suffering from chronic heartburn and gastroesophageal refluxoften experience BE as a result of stomach acid passing through LES 16and into the lower part of esophagus 14. Patients who are suffering fromBE can be detected by determining whether the inner surface of the lumencomprising esophagus 14 has changed from its normal light pink color toa dark pink color in a region 18 that is just above LES 16. Theexemplary scanning capsule enables region 18 within esophagus 14 to bereadily scanned, producing images in which the presence of the darkerpink color of the inner surface that is indicative of BE is clearlyapparent. More importantly, as discussed in further detail below, it iscontemplated that the scanning capsule may enable the scanning processto be carried out in an automated fashion, so that the detection of BEcan be accomplished by a medical practitioner such as a technician or anurse who is trained in the procedure, and normally, without any directinteraction by a medical doctor.

The manner in which an esophagus can be scanned is illustrated in FIG.1B. As shown therein, a capsule 20 that is sized and configured for thispurpose has been advanced through the interior of esophagus 14 and hasjust passed into stomach 12. Capsule 20 is coupled to a tether 22 thatextends up through esophagus 14 and out through a patient's mouth. Ahousing 24 of the capsule is about the size of a large vitamin pill,e.g., about 15 mm long by 7 mm in diameter and comprises a plasticmaterial that is biocompatible and not affected by stomach acid or otherbiological fluids. Tether 22 is extremely flexible and is relativelysmall in diameter, e.g., about 1 mm. Within housing 24, capsule 20includes an actuator 28 that drivingly moves a scanner 26 to scan aninner surface of the lumen within a field of view (FOV) 30. When used todetermine if a patient has BE, capsule 20 will typically be drawn backpast LES 16 so that FOV 30 encompasses region 18. An image of region 18that is provided by scanner 26 can thus be evaluated to indicate whetherthe tissue on the inner surface of esophagus 14 has turned the darkerpink color indicative of BE. It will also be apparent that the innersurface of esophagus 14 can be scanned and imaged as capsule 20initially descends toward stomach 12.

FIG. 2 illustrates further details of this embodiment of capsule 20; anumber of other exemplary embodiments of the capsule are discussedbelow. A forward or distal end 32 of housing 24 is opticallytransparent, so that light emitted by a vibrating optical fibercomprising scanner 26 in this exemplary embodiment, can pass through anoptical system 34 that includes a plurality of lenses, reaching theinner surface of the esophagus or other lumen in which capsule 20 isdisposed. While the inner surface may be illuminated by scanner 26 usingother wavebands of light, in this exemplary embodiment, the innersurface of the lumen is illuminated using white light. Light reflectedfrom the inner surface is detected by a plurality of red, green, andblue (RGB) sensors 36 r, 36 g, and 36 b, respectively. The white lightthat is used to illuminate the inner surface of the esophagus or lumenis conveyed to scanner 26 through an optical fiber (not separatelyshown) disposed within tether 22. The signals produced by the pluralityof RGB sensors are conveyed back through electrical leads (not shown)within tether 22 for processing to produce an image corresponding to theportion of the inner surface that was scanned. In an alternativeexemplary embodiment discussed below, the light reflected from the innersurface is conveyed proximally through optical fibers in the tether todetectors that are external of the patient's body.

The exemplary embodiment of FIG. 2 also includes position sensors 38,which respond to an external signal provided by a signal source (notshown) external to the body of the patient, by producing a signalindicative of a location, and optionally, an orientation of capsule 20within the patient's body. A suitable position sensor, which responds toelectromagnetic signals, is available, for example, from AscensionTechnology. Position sensors 38 can respond to an electromagnetic field,an RF signal, a light signal of a wavelength selected to penetratetissue and pass into the lumen, or another appropriate signal.Alternatively, it is also contemplated that position sensors 38 can bereplaced by a signal source, which is used in connection with anexternal sensor (not shown) to determine the location, and optionally,the orientation of capsule 20 within a patient's body. The externalsignal source or position sensor can be disposed at a specific locationon the body of a patient to provide a reference, by strapping the signalsource or position sensor to a patient's torso at the specific location.

A chemical sensor 40 is optionally included to sense a chemicalparameter. For example, chemical sensor 40 can detect hydrogen ionconcentration, i.e., pH, within the lumen. Alternatively oradditionally, the chemical sensor can include a temperature sensor formonitoring an internal temperature of the lumen. Similarly, a pressuresensor can be employed in addition to or in place of chemical sensor 40,which is thus intended to represent any one or all of these sensors.

As a further option, a selectively releasable connection 42 can beprovided to pneumatically or electrically disconnect the capsule fromthe tether when desired. When thus released from its connection with thetether, the capsule will be conveyed through the body lumen and if thelumen is involved with the digestive tract, the capsule will passthrough and be expelled. The releasable connection can be activated witha pressurized pulse that is propagated through a lumen (not shown) intether 22 from an external source (not shown), or can be an electricalsignal that magnetically actuates releasable connection 42 using anelectrical current provided through a lead in the tether. A similarreleasable joint might also or alternatively be provided near theproximal end of the tether, to release the tether and capsule to pass onthrough the lumen together.

System Processing Overview

FIG. 3 illustrates a system 50, with external instrumentation, forprocessing the signals produced by various components that are insidethe capsule and indicates how signals used for controlling the systemare input to these components. In order to provide integrated imagingand other functionality, system 50 is thus divided into those componentsthat remain external to the patient's body, and those which are in thecapsule (i.e., the components within a dash line 52, some of which areoptional depending upon the application in which this invention is beingused). A block 54 thus lists the functional components that can bedisposed within the capsule. As indicated in the Figure, thesecomponents include illumination optics, one or more electromechanicalscan actuator(s), one or more scanner control actuator(s), one or morescanner motion detector(s) for control of the scanner motion, photondetectors for imaging a region of interest (ROI) (these photon detectorscan alternatively be disposed externally if a light path is provided inthe tether to convey the light reflected from the inner surface of thelumen to external detectors), and optionally, additional photondetectors for diagnostic purposes and for therapy and monitoringpurposes (which can also be disposed externally of the capsule andpatient). It should be noted that in regard to system 50, only thefunctional components actually required for a specific application, suchas imaging an esophagus, may be included. Also, the additional functionsbesides imaging can be diagnostic, or therapeutic, or a combination ofthese functions, and can include taking a biopsy of tissue at aninternal site for subsequent evaluation by carrying out an appropriatelaboratory procedure. Although a specific embodiment of the capsule isnot shown that includes a plurality of actuators, each associated with adifferent scanner, it will be apparent that due to the relatively smallsize of the scanners disclosed herein, it is possible to provide anarray of such scanners to increase the total area scanned. Each suchscanner will be provided with its own actuators and either withdetectors to detect light from the region scanned by that scanner orwith a waveguide to convey the light to one or more external detectors.

Externally, the illumination optics are supplied light from illuminationsources and modulators, as shown in a block 56. Further detailsconcerning several preferred embodiments of external light sourcesystems for producing RGB, UV, IR, and/or high intensity light conveyedto the distal end of an optical fiber system are disclosed below. Ablock 58 indicates that illumination sources, modulators, filters, anddetectors are optionally coupled to the electromechanical scanactuator(s) within the capsule, and/or to the scanner control actuatorsprovided in the capsule. Scanner motion detectors are optionally usedfor controlling the scanning and produce a signal that is fed back tothe scanner actuators, illumination source, and modulators to implementmore accurate scanning control, if needed.

In a block 60, image signal filtering, buffering, scan conversion,amplification, and other processing functions are implemented using theelectronic signals produced by the imaging photon detectors and for theother photon detectors employed for diagnosis/therapy, and monitoringpurposes. Blocks 56, 58, and 60 are interconnected bi-directionally toconvey signals that facilitate the functions performed by eachrespective block. Similarly, each of these blocks is bi-directionallycoupled in communication with a block 62 in which analog-to-digital(A/D) and digital-to-analog (D/A) converters are provided for processingsignals that are supplied to a computer workstation user interfaceemployed for image acquisition and processing, for executing relatedprograms, and for other functions. The computer workstation can beemployed for mass screening of the population when programmed to processimages produced by scanning inside an esophagus to detect BE so thatnear real-time results are provided, and normally without requiring aphysician's evaluation.

Control signals from the computer workstation are fed back to block 62and converted into analog signals, where appropriate, for controlling oractuating each of the functions provided in blocks 56, 58, and 60. TheA/D converters and D/A converters within block 62 are also coupledbi-directionally to a block 64 in which data storage is provided, and toa block 66. Block 66 represents a user interface for maneuvering,positioning, and stabilizing the capsule with the scanner inside a lumenwithin a patient's body. Further description of several exemplarytechniques for determining a location of a capsule in a lumen arediscussed below. The procedure for maneuvering and positioning thecapsule in a lumen is discuss in further detail below. Also discussed isa technique for stabilizing the capsule in the lumen.

In block 64, the data storage is used for storing the image dataproduced by the detectors within a patient's body, and for storing otherdata related to the imaging and functions implemented by the scanner inthe capsule. Block 64 is also coupled bi-directionally to the computerworkstation and to interactive display monitor(s) in a block 70. Block70 receives an input from block 60, enabling images of the ROI on theinner surface of the lumen to be displayed interactively. In addition,one or more passive video display monitors may be included within thesystem, as indicated in a block 72. Other types of display devices, forexample, a head-mounted display (HMD) system, can also be provided,enabling medical personnel to view an ROI in a lumen as a pseudo-stereoimage.

FIG. 4 illustrates one exemplary embodiment of a scanner 120 that can beused in the capsule. Scanner 120 includes an electromechanical device orpiezo-ceramic tube actuator 122 that causes a first mode of vibratoryresonance in a cantilevered optical fiber 124. In this exemplaryembodiment, the cantilevered optical fiber includes a collimating lens126 at its distal end and a scan lens 128 that directly focuses theoptical beam of light that has passed through the collimating lens ontoan illumination plane 132, which typically would comprise a region onthe inner surface of a lumen. Light focused by scan lens 128 forms apoint spread function (PSF) 134 on illumination plane 132 and as thecantilevered optical fiber moves, a PSF 134′ moves over the illuminationplane. Although cantilevered optical fiber 124 can be limited toscanning along a single axis as indicated by arrows 130, it is typicallypreferable to use an actuator that moves the optical fiber so that itscans two-dimensionally, e.g., in a spiral pattern. However, at a highamplitude resonance vibration produced by a linear single axis actuator,the resulting motion of the optical fiber can be in two dimensions dueto nonlinear cross-coupling of mechanical forces. Thus, two axisactuators are not required for two-dimensional (2-D) scanning.

FIG. 5 graphically illustrates an advantage of the scanners used in thepresent invention. Such fiberoptic scanners are readily capable ofachieving a 120° FOV by imaging the scanned point-source object plane toa magnified image plane, which typically would comprise a region on theinner surface of a lumen. In contrast to FIG. 4, which illustratesoptical beam scanning, FIG. 5 depicts an exemplary embodiment of pointsource imaging that uses imaging lenses rather than the combination of amicrolens and a scan lens. FIG. 5 also illustrates the relative Gaussianbeam diameters of the light used for illumination, at different anglesbetween zero and 45°, for one exemplary embodiment of an optical system140 that includes lenses 142 and 144. In this embodiment, detection ofreflected light is carried out using optical detector 146 that isdisposed on and around the outer periphery of lens 144 (this portion ofthe lens does not transmit the illumination light), or alternatively,light reflected from the region being scanned can be collected andconveyed through optical fibers to external detectors (not shown). Whileshown in cross-section, it will be understood that optical detector 146wraps around the entire periphery of lens 144 and actively detects lightboth on its forward surface and on all sides, as indicated by thehatched light sensing portions thereof.

FIGS. 6A and 6B illustrate embodiments of 2D scanning point-sourceilluminator 240 and optical beam illuminator 240′ for use in thecapsule. In FIG. 6A, point-source illuminator 240 has the capability ofproviding a point source illumination through an optical fiber 242within a capsule that is caused to scan an ROI on the inner surface of alumen within a patient's body. Light emitted by the scanning opticalfiber is transmitted through imaging lenses 244 a, 244 b, and 244 c toilluminate different portions of the ROI as the point source provided bythe scanning optical fiber is caused to move in a desired pattern withinthe capsule (not shown). In the position illustrated with solid lines, alight beam 246 illuminates a particular portion of the ROI, while in theposition illustrated by dash lines, the scanning optical fiber produceslight beam 246′ that illuminates a different portion of the ROI. Lightreflected from each successive point illuminated by the scanning opticalfiber is reflected back through imaging lenses 244 c, 244 b, and 244 aand is received by RGB photon detectors 245 r, 245 g, and 245 b,respectively, which produce corresponding electrical signals that aretransmitted outside the patient's body for use in displaying a fullcolor image of the ROI. Alternatively, the light can be conveyed throughthe tether to external photon detectors disposed outside the patient'sbody.

In addition, therapy can be rendered to the inner surface of a lumenusing scanning optical fiber 242. For example, by illuminating thepoints scanned by it using a relatively high powered laser, highintensity light for the purposes of drug activation or photodynamictherapy (PDT), or thermotherapy can be applied to the ROI. Since thesignals produced by the RGB photon detectors correspond to successivepoints in the ROI, the image resulting from the signal that they produceis based upon a time series accumulation of image pixel data. Scanningoptical fiber 242 is preferably a single mode or hollow optical fiber,of telecommunications grade or better. One significant advantage of thisintegrated system is that the mechanisms employed for generating thevisual image are the same used for diagnostic, therapeutic, and surgicalprocedures. The directed optical illumination employed for imageacquisition enables the most sophisticated diagnoses and therapies to beintegrated into this single imaging system within a capsule sized topass through a body lumen (by sharing the scan engine, display, and userinterface).

FIG. 6B illustrates a scanning optical beam illuminator 240′ for use ina capsule (not shown) and which also includes scanning optical fiber242, just as the exemplary embodiment shown in FIG. 6A. However, insteadof using imaging lenses, scanning optical beam illuminator 240′ employsa collimating lens 243 that is attached to the distal end of thescanning optical fiber and a scan lens 244′. The light conveyed throughoptical fiber 242 as it moves within the capsule is collimated bycollimating lens 243 and then focused onto a flat illumination plane 233b, or a curved illumination plane 233 c, corresponding to the ROI on theinner surface of a lumen within a patient's body. Light reflected fromeach successive point that is scanned as the scanning optical fibermoves passes back through scan lens 244′ and is detected by RGB photondetectors 245 r, 245 g, and 245 b, which respectively provide the RGBsignals over lines 248 that are used to produce an image, with dataaccumulated pixel-by-pixel.

At the illumination plane, the beam of optical radiation is focused toachieve maximum intensity and/or optical quality, which is the goal forall modes of scanning When tissue is coincident with the illuminationplane, the optical irradiance is a function of the optical power andsize of the light spot on the tissue. Thus, with regard to imaging,diagnoses, and therapy, the resolution of the scanner disposed in thecapsule is determined by this spot size at the image plane and may alsobe limited by the sampling density (i.e., samples per unit area oftissue), since higher resolution is achieved by providing more scanlines per area. With regard to image acquisition, the image resolutionis determined by the illumination spot size, detector bandwidth (andscan rate), and signal-to-noise ratio (illumination intensity andcollection efficiency), while image resolution is not limited by thephysical size or number of the photon detectors.

Since diagnoses and therapies require accurate spatial discrimination,there is a need for directed illumination that is pre-calibrated beforedelivery. By integrating the optical imaging with diagnostic andtherapeutic scanning delivered in a capsule, a medical practitioner caneasily see the spatial discrimination of the optical scanning by viewingthe displayed image before proceeding to diagnostic or therapeuticapplications within the lumen in which the capsule is disposed. Finally,the integration of computer image capture electronics and imageprocessing software enables the image, diagnostic, and therapeutic datato be analyzed on a pixel-by-pixel basis. Since each pixel correspondsto the same area or volume of tissue, the single fiber integrated systemmaintains spatial registration for all three functions; imaging,diagnosis, and therapy. Consistent spatial registration from the samepoint of view for all three functions makes the single optical fiberscanning system, delivered within a capsule passing through a lumen,highly accurate and easy to use by medical practitioners.

The advantages afforded by using the scanning device integrated within arelatively small capsule are:

-   -   Smaller size with integration;    -   Little or no sedation of the patient;    -   Physician is not required to insert the tethered capsule into a        patient's esophagus;    -   Lower cost with integration and use of low cost components;    -   Lower flexural rigidity to allow greater access within various        lumens in the body;    -   Faster procedural times, especially if requiring reiterations of        therapy;    -   Greater accuracy with integrated high-resolution imager and        interactive display;    -   Additional features with scanning optical system, such as        variable resolution (real-time zooming) and enhanced stereo        effects (such as shading);    -   Additional functionality with integrated non-visible optical        sources and detectors;    -   Lower risk to patient for infection from multiple tools or        multiple insertions within a lumen;    -   Faster recovery times for patient with less healthy tissue        damage; and    -   Able to be left inside the body for extended periods of time to        monitor chronic diseases.

FIG. 6C illustrates a portion of a concentric optical fiber assembly 280for use as a confocal scanner that is readily employed with the capsuleof the present invention. Optical fiber assembly 280 includes arelatively small central optical fiber 284, which is surrounded bycladding 286. A larger diameter optical fiber surrounds the smalleroptical fiber. Illumination of an ROI is provided through small diameteroptical fiber 284, and light emitted thereby passes through lenses 288a, 288 b, and 288 c to illuminate the ROI. Light reflected or otherwisereceived from the ROI is focused by these lenses back into an opticalfiber assembly 289, which conveys the light that is received, throughthe tether, to detectors and other instrumentation disposed outside thepatient's body. It should be noted that a single optical fiber can bothilluminate the ROI and convey light from the ROI to the externalinstrumentation in this so-called concentric confocal imaging. Theconcentric optical fiber geometry is a single mechanical unit eitherfused together upon heating pulling from a preform, or alternatively,the concentric regions of refractive index differences can bemanufactured by doping the glass fiber radially. A tubular piezoelectricactuator 282 causes the concentric optical fibers to move together andthus to scan the ROI in one of the modes described above. The lightcollected in the surrounding optical fiber can be used with signals fromdetectors or optical fibers at radially increasing distances from thereflected confocal point to enhance image analysis and refine the depthof light penetration for diagnosis, imaging, and therapy. In extremelyhigh-gain or discrimination detection configurations, the backscatteredlight may be collected in the same part of the waveguide (e.g., the coreof the optical fiber). Such applications will use the optical coherenceproperty to amplify the small signal level, producing diagnostic mapsbased upon optical coherence reflectometry (OCR) or optical coherencetomography (OCT), or laser-induced feedback.

FIGS. 6D and 6E illustrate an embodiment of a scanner useful within thecapsule of the present invention, which includes detectors for RGB,ultraviolet (UV), and infrared (IR) spectral components. An opticalfiber assembly 295 includes an internal actuator 291 mounted on asupport 293 within the capsule (not shown). An optical fiber 300enclosed within the housing having an opening 298 extends distally ofactuator 291 and is moved by the internal actuator, which is preferablya tubular piezoelectric type, so as to achieve a desired scanningpattern, such as a helical or spiral scan. RGB detectors 292 and 294 aredisposed above and below optical fiber 300, while RGB detectors 306 and308 are disposed to the left and right of the optical fiber, asillustrated in FIG. 6E. In addition, RGB detectors 290 and 296 aredisposed on the outer surface of the assembly on the top and bottomthereof, as indicated in these Figures. In a similar manner, RGBdetectors 302 and 304 are mounted on the left and right sides of thedetector as illustrated in FIG. 6E. UV detectors 310 and 312 are mountedon one of the diagonals between the RGB detectors, while IR detectors314 and 316 are mounted on the other diagonal. Accordingly, apseudo-stereo image can be produced in regard to the RGB, UV, or IRspectral components received by the various detectors included on thisassembly, when imaging tissue on the inner surface of a lumen, fromwithin the capsule of the present invention. By comparing signals fromthe multiple RGB detectors and knowing the orientation of the tetheredcapsule within the lumen, the level of the signal due to specularreflection and multiple scattering can be estimated and reduced byappropriate signal processing.

FIGS. 6F and 6G illustrate an optical fiber assembly 295′ in whichparallel and perpendicular polarized light detectors are included.Optical fiber 300 conveys light that is polarized in a paralleldirection as indicated by reference numeral 328. On opposite sides ofoptical fiber 300 are disposed parallel polarized light detectors 334and 336, while above and below optical fiber 300 are disposedperpendicular polarized light detectors 324 and 326, as shown in FIG.6G. In addition, perpendicular polarized light detectors 320 and 322 aredisposed above and below perpendicular polarized detectors 324 and 326,while parallel polarized light detectors 329 and 330 are disposed leftand right of parallel polarized light detectors 334 and 336. Opticalfiber assembly 295′ is thus usable within a capsule to detect polarizedlight in both orientations, where the light is reflected or otherwisereceived from an ROI on the inner surface of a lumen, for analysis byinstrumentation disposed external to the patient's body that receivesthe detector output signals through the tether that is coupled to thecapsule (neither shown in these Figures). The signal produced by thevarious polarized light detectors can also be used for producing animage of the tissue inside the lumen, corresponding to that specifictype of polarization, for display externally. By recording light that isshifted in polarization due to interaction with the tissue, specularreflection can be minimized. Since the degree of polarization from thetissue partially depends on tissue optical properties, various tissuetypes and depths can be discriminated by measuring both axes ofpolarization.

FIG. 7A illustrates an exemplary scanning and detection system 266 thatcan be used with a capsule for providing both a pseudo-stereo image ofan ROI on the inner surface of a lumen and for acquiring a spectralimage that can be analyzed with a spectrophotometer externally of thelumen. In this system, an optical fiber assembly 250, which comprisesthe tether extending through the lumen and outside the patient's bodyincludes an optical fiber 256 that is tapered at its distal end and issurrounded by a piezoelectric actuator 254. Actuator 254 causes opticalfiber 256 to vibrate and scan an ROI, emitting light that passes throughlenses 258 a and 258 b to illuminate the inner surface of the lumen (notshown). Light reflected from the ROI from this tissue or light otherwisereceived therefrom (such as phosphorescent or fluorescent emissions) iscollected by twelve optical fibers 252 that are arranged in acircumferential array around optical fiber 256. As illustrated in thisexemplary embodiment, optical fibers 1, 2, and 3, which are collectivelyreferred to by a reference number 260, are respectively coupled throughthe tether to external RGB imaging detectors corresponding to a leftside of the circumferential array. Similarly, optical fibers 7, 8, and9, which are collectively identified by a reference number 262, arerespectively coupled through the tether to external RGB imagingdetectors for the right side of the circumferential array. Another setof optical fibers 264 are coupled through the tether and connected to aspectrophotometer 270. The spectrophotometer is employed for spectralanalyses and spectral image acquisition using UV, visible, and/or IRlight. Since the RGB detectors for the left and right side of thecircumferential array receive light from the ROI at two spaced-apartportions of the array (i.e., the left and right sides), they produce apseudo-stereo full color image that is readily viewed using an HMDdisplay (not shown).

A schematic diagram illustrating an exemplary light source system 340for producing light of different spectral composition that is coupledthrough the tether and into an optical fiber 360 disposed within thecapsule is illustrated in FIG. 7B. In this embodiment, a red lightsource 342, a green light source 344, a blue light source 346, and an UVlight source 348 are each selectively coupled into optical fiber 360.Optical fiber 360 extends through the tether so that the distal end ofthe optical fiber emits light to illuminate tissue on the inner surfaceof a lumen through which a capsule that includes the distal end of theoptical fiber is passing. Attenuators 350 are provided at the proximalend of the optical fiber for each of the light sources so that theintensity of the light they produce can be selectively controlled. Threedichroic mirrors 352, 354, and 356 that include coatings specific to thecolor of light emitted by each of the corresponding green, blue, and UVlight sources are positioned within the light path to reflect green,blue, and UV light, respectively, into the proximal end of optical fiber360. Light that is outside the reflectance waveband for each of thesedichroic mirrors is passed through the dichroic mirror and is focused bya lens 358 into the proximal end of optical fiber 360.

An alternative light source system 362 for use with the presentinvention is illustrated in FIG. 7C. In this embodiment, red, green, andblue light sources 342, 344, and 346, respectively, are coupled throughoptional attenuators 350 to a series or sequence of optical couplers 366through lenses 364. Lenses 364 focus the light from each of thedifferent colored light sources into optical fibers 365, which conveythe light to optical couplers 366. In addition, an IR source 368transmits light through an optional attenuator 350 and a lens 364 intooptical fiber 365, which conveys the IR light to the last opticalcoupler in the sequence. Optical detectors 369 are provided formonitoring the light intensity levels or power levels for each of thedifferent sources of light, enabling the intensity of the various lightsources to be controlled. From the last optical coupler, an opticalfiber 367 conveys light to an input to optical detectors 369, while theoutput from the last optical coupler is input to the proximal end ofoptical fiber 360 for input through to the scanner disposed within acapsule in a lumen inside a patient's body (neither the tethercomprising optical fiber 360 or the capsule are shown—to simplify thisdrawing).

As indicated above, it is desirable to develop a scanning device with asmall cross-sectional area that can be manufactured at relatively lowcost and high volume to ensure that the endoscopic capsule scanningsystem is economical and thereby facilitate its widespread use.Microelectromechanical systems (MEMS) technology using an integratedthin film device may be beneficially employed when producing economicalscanners to more readily achieve this goal. FIGS. 8A, 8B, and 8Cillustrate an exemplary thin film optical system 370 that can be adaptedfor use as a scanner within a capsule for use in scanning applications.A further exemplary alternative 370′ illustrated in FIG. 8D includesparallel cantilevered thin film optical waveguides for scanning anddetectors.

In this thin film exemplary embodiment of a scanner, electrostaticactuators 386 act on a thin film optical waveguide 380, which issupported on a raised ledge 378. The thin film optical waveguide is onlyabout 0.003 mm in diameter. A distal portion 382 of the thin filmoptical waveguide is caused to scan in the two orthogonal directionsindicated by the curved arrows in FIGS. 8A and 8B. It should be notedthat the scanning motion can be one-dimensional (i.e., along a singleaxis), or as shown, in two dimensions (e.g., following either a rasterpattern or a spiral pattern). Optionally, the thin film optical devicecan be mounted in the capsule on a rod 373, which is then manually ormechanically rotated or vibrated to change the orientation or displacethe single axis scan. Also provided is a lens 384 that can be mounted toa silicon substrate 376 (or other substrate material). As analternative, actuators (not shown), which are external to the substratebut still disposed in the capsule, can be used instead of theelectrostatic actuators, in which case, an optical fiber 374 and lens384 would be supported by silicon substrate 376. The optical fiber wouldbe caused to vibrate by the external actuators, causing the cantileveredthin film optical waveguide to resonantly scan as desired pattern.

Optical fiber 374 can be affixed to silicon substrate 376 within acentering V notch 390 to ensure that it is aligned with thin filmoptical waveguide 380. Since the optical fiber is approximately 0.1 mmin diameter, care must be taken to provide accurate alignment betweenthe ends of the optical fiber and the thin film optical waveguide. FIGS.8A and 8B show an exemplary embodiment using butt-end coupling betweenoptical fiber 374 and a thin film optical waveguide 380. To ensureappropriate alignment between the optical fiber and the thin filmoptical waveguide, V notch 390 precisely establishes a disposition ofthe optical fiber relative to the thin film optical waveguide. Anindex-matching gel 375 or fluid can be used to couple light from opticalfiber 374 to thin film optical waveguide 380. To reduce the gap filledby index-matching gel 375, the tip of the optical fiber can be etched toform a taper. Further, the tip length and surface can be adjusted by CO₂laser machining before affixation. Other embodiments of the MEMS scannerdescribed below further alleviate alignment problems.

In the embodiments shown in FIGS. 8A, 8B, and 8C, light reflected backfrom a target in the ROI passes through lens 384 and is received by RGBdetectors 392 r, 392 g, and 3926 b, respectively. These detectors,disposed in the capsule, respond to the light of the correspondingcolor, producing a signal that is conveyed proximally to the externalcomponents, as discussed above. In FIG. 8D, separate image anddiagnostic/therapeutic thin film optical waveguides are spaced apart andscanned in parallel; this exemplary embodiment uses a diagnostic “DIAG”detector 392 d.

Automated System for Mass Screening

One of the contemplated uses of the present invention is that it mighteventually enable a nearly automated esophageal screening process to becarried out by a medical practitioner (not requiring that the procedurebe done by a medical doctor) to screen a patient for BE. FIG. 9illustrates an automated system for use in connection with the presentinvention for conducting scanning of the inner surface of the esophagusof a patient 395 by a medical practitioner 408, to determine if thepatient is afflicted with BE (or some other condition of the esophagus).This system includes a computer processor 394, which carries out many ofthe functions discussed above in connection with FIG. 3 and in furtherdetail below.

Tether 22 is coupled to computer processor 394 after passing through anon-contact axial motion measuring device 396 that is used formonitoring the movement of tether 22. As explained above, tether 22 isused for refracting or enabling advancement of a capsule within theesophagus of patient 395. An electrical cable 402 conveys a signalproduced by non-contact axial motion measuring device 396 that isindicative of the position or axial movement of the tether, to computerprocessor 394. Tether 22, which includes one or more optical fibers andone or more electrical leads that convey optical and electrical signalsto and from the scanner disposed in the capsule (neither shown in thisview), is refracted or allowed to advance in the esophagus with thecapsule. The tether extends between lips 404 and down the esophagus ofthe patient. Indicia (e.g., magnetic or optical as described in detailbelow, enable the position and movement of the tether to be detected asthe tether passes through device 396. Patient 395 is initially provideda glass 406 of liquid, such as water, to facilitate swallowing thecapsule and attached tether 22. The liquid is swallowed after thecapsule is inserted into the patient's mouth and helps to advance thecapsule through the esophagus with the normal peristalsis of the musclescomprising the walls of the esophagus as the patient swallows theliquid.

The capsule is allowed to advance into the stomach of the patient and isthen withdrawn past the LES by medical practitioner 408 grasping handle402 and rotating reel 396. Additionally, it is possible that acomputer-controlled withdrawal of the capsule might use a motorized reel(not shown) to fully automate the screening process by withdrawing thecapsule up through the esophagus. Thus, the computer might determine howfast to withdraw the capsule, in response to criteria that determine thequality and content of the images being scanned by the capsule in realtime, and in response to the signal output from non-contact axial motionmeasuring device 396. In addition to controlling the speed of thewithdrawal of the capsule, the computer can control the intensity oflight provided for scanning and patient-specific variables, and cancarry out automated image stitching to form panoramic images of theinterior surface along a length of a lumen. An example of currentlyavailable automated image stitching software is available, for example,from Matthew Brown as “AutoStitch,” (see the URL regarding this softwareat http://www.cs.ubc.ca/-mbrown/autostitch/autostitch.html). Such imagescan be used in connection with image recognition software to determinethe location of the LES and to automate the determination of whether apatient has BE or some other medical problem. Also, images automaticallystitched together to form a full 360° panoramic view can be calibratedto form a ruler-like measure in pixels of the length of the capsule fromthe LES, as an alternative measure to define the location of the capsulein a patient's esophagus. As a further alternative, the signal producedby non-contact axial motion measuring device 396 may be employed tospeed up the process of stitching together the successive axial imagesof a lumen such as the esophagus, to form the full continuous panoramicimage of the lumen.

By viewing a display 398 that is coupled to computer processor 394, themedical practitioner can readily observe images of the stomach and then,as the reel rewinds the tether to retract the capsule above the LES, themedical practitioner can observe images of the inner surface of theesophagus on the display. An indicator 400 b is displayed at one side ofthe display to show the relative speed and direction with which thecapsule is moving through the esophagus.

Computer processor 394 can detect the LES based upon the changes in animage 399 and display a distance 400 a of the capsule above the LES, andcan be programmed to automatically evaluate the images of the portion ofthe inner surface of the esophagus immediately above the LES todetermine if the patient has the characteristic dark pink color at thatpoint, which is indicative of BE. The medical practitioner should onlybe required to manipulate tether 22 and assist the patient in initiallyswallowing the capsule, since the results of the image scanning processcan thus be sufficiently automated to detect the condition of theesophagus in near real time, providing an immediate indication ofwhether the patient is afflicted with BE. The efficiency of such asystem should thus enable mass screenings of the population to beconducted at minimal cost, so that esophageal cancer of which BE isoften a precursor, can be avoided by early detection of BE.

Functional Block Diagrams

FIG. 10 illustrates at least some of the variety of functions that canbe carried out with the exemplary scanning system when the capsule isdisposed within a lumen of a patient's body. Functions such asdiagnosis, therapy, and monitoring are shown in blocks that are formedwith dash lines, while solid lines are used for imaging functions of asystem 410 that is implemented with the capsule and related components.As illustrated in this Figure, imaging lasers 412 produce light that isdirected into a patient's body via the tether and directed by thescanner in the capsule, through imaging optics used with the scanningoptical fiber that is disposed in the capsule. Furthermore, diagnostic,therapeutic, and monitoring lasers in a block 416 that can be controlledby a remote optical switch and attenuators in a block 418 producecoherent light conveyed through an optical coupling mechanism 420 toadditional optical components 422 disposed inside the capsule for usewithin the lumen of a patient's body. RGB photon detectors 430 respondto light received from the ROI on the inner surface of the lumen,producing an electrical signal that is conveyed through electricalconductors within the tether or running alongside it, to instrumentationdisposed outside the patient's body. Alternatively, the RGB light can beconveyed through optical fibers within the tether to external photondetectors 426 outside the body, or to other types of optical detectors424 that include, for example, photodiodes and related circuitry.

As indicated in a box 432, the exemplary system may include additionalhigh or low power UV, and/or visible, and/or IR detectors associatedwith collection optical fibers for use by one or more spectrophotometersor spectrum analyzers. For example, spectrophotometers and spectrumanalyzers indicated in a block 434 can receive light conveyed throughlight collection optical fibers and/or as signals conveyed overconductors as indicated in a block 436. The system may includeadditional photon detectors disposed inside the capsule within thepatient's body as a further option. Signals are exchangedbi-directionally between block 432 and 434 and a computer processor (orworkstation) and data acquisition component in a block 440. The computerprocessor can execute algorithms that provide for non-linear scanningpatterns and control algorithms and also can be programmed to carry outintensity data acquisition, image mapping, panoramic image stitching,and storage of data. In addition, tasks including real-time filtering(e.g., correction for motion and scanner artifacts), real-timedetermination of ratios and background subtraction, deconvolution,pseudo-stereo enhancement, and processing of the signals produced by thevarious detectors are implemented by the computer processor. Signalsprovided by the computer processor are output to image display devices(such as shown in FIG. 9) and for data storage on non-volatile storage(not shown). The image display devices may include cathode ray tube,liquid crystal displays, and HMD devices or other types of stereographicdisplays, as noted in a block 442.

Since commercially available displays typically require rectilinearvideo format, any non-rectilinear optical scanning patterns must bestored in data buffers (memory) and converted to the standard rasterscanning format for the display monitors, to make use of the manyadvantages of non-rectilinear scanning, (such as a simplified singleactuator, cylindrical scanner size, and lower scanning rates) used forthe one or more scanners in the exemplary capsule. This additional stepin signal conditioning and remapping is technically trivial withprogrammable computing devices.

In addition, image analysis software for carrying out spectral andmultivariate analysis and for locating and calculating the limits ofregions of interest are carried out using the computer processor orother computing device. In regard to the ROI on the inner surface of thelumen, the computations may determine its distribution, boundary,volume, color, and optical density, and based upon the data collectedfrom the ROI, can determine a tissue disease state such as BE, andmedical staging, as well as calculate and monitor therapeutic dosage.All of these functions are indicated in a block 444, which may use thenormal imaging computer processor of block 440. Block 444 is coupled toa block 446, in which additional interactive displays and image overlayformats are provided. Associated with block 444 is a block 448, whichindicates that scanner power and control electronics are provided foractuating the electromechanical scanner and for receiving signals fromservo sensors in a block 450, which are used for both normal imageacquisition and enhancements involved in screening, monitoring, anddiagnosis, as well as pixel accurate delivery of therapy to a desiredsite within the lumen.

Various embodiments of optical fiber scanning actuators have beendescribed above, in connection with moving a scanner disposed in thecapsule to image an ROI within a lumen. A block 454 indicates thatprovision is made for manual control of the distal tip of the scanningoptical fiber, to enable the capsule containing the scanning opticalfiber to be inserted into a patient's body and positioned at a desiredlocation adjacent an ROI. The manual control will perhaps includeturning the tether to rotate the capsule and/or axially positioning thecapsule and scanner relative to the ROI in the lumen, and possiblyemploying automated servo sensors, as indicated in a block 456 tofacilitate the positioning of the capsule and one or more scanners atthe desired location. Once positioned, automatic vibration compensationfor the scanner can be provided, as noted in a block 452, to stabilizethe image in regard to biological motion (breathing and cardiovascularmovement) and physical movement of the patient. In addition, othermechanisms can be provided in at least one exemplary embodiment, forstabilizing the capsule where desired within the lumen of a patient'sbody.

Details of the various functions that can be implemented with thecapsule imaging system are as follows:

Integrated Imaging, Screening, and Diagnosis

-   -   Optical tissue imaging using UV, visible, and IR wavelengths;    -   Fluorescence imaging using UV, visible, and IR wavelengths;    -   Thermal imaging using IR wavelengths;    -   Deep tissue imaging using IR wavelengths;    -   Concentric confocal and true confocal imaging;    -   Imaging through blood using IR wavelengths;    -   Polarization-contrast imaging;    -   Laser feedback microscopy;    -   Optical coherence tomography (OCT) and reflectometry (OCR);    -   Optically stimulated vibro-acoustography analysis;    -   High resolution and magnification tissue-contact imaging;    -   Laser-induced fluorescence (LIF) and ratio fluorescence imaging        and detection;    -   Multi-photon excitation fluorescence imaging;    -   Fluorescence lifetime imaging and analysis;    -   True sizing of imaged structures using stereo and range finding        options;    -   Laser-induced fluorescence spectroscopy (LIFS);    -   Raman spectroscopy analysis;    -   Elastic scattering spectroscopy (ESS) analysis;    -   Absorption spectroscopy;    -   Detection and mapping of chemi-luminescence and cell viability;    -   Spatial mapping of optical sensor data (oxygen concentrations,        pH, ionic concentrations, etc.);    -   Temperature measurement and feedback control;    -   Guidance of pressure measurements (manometry) and correlation of        visual and manometric observations of the esophagus, lower        esophageal sphincter, stomach, pylorus, small intestine and        other body lumens; and    -   Other measurements such as color, laser power delivery, tissue        properties, photobleaching, and photocreation of compounds for        monitoring and feedback control.

Therapies, Surgeries, and Monitoring

-   -   Photodynamic Therapy (PDT);    -   Heating of tissue and/or tumors, (e.g. hyperthermia treatment);    -   Laser surgery from optical illumination (UV, heat, and/or        ablation)    -   Photoactivated chemistry, photopolymerization, and implantation        of biomaterials;    -   Laser cauterization; and    -   Mechanical destruction of tissue using shock waves produced by        absorption of pulsed optical radiation.

Interactive Displays & Advanced User Interface Design

-   -   Quasi-stereo on display monitors, stereographic mapping using        pseudo color overlay, and true 3D display formats (Note:        Individual display strategies and capabilities depend on the        specific application); and    -   Interactive touch/point screen.

FIGS. 11A and 11B illustrate the different functions that can be carriedout with the capsule, depending upon the instrumentation that is used inthe scanning system. FIG. 11A shows a single scanning waveguide used forimaging, sampling diagnoses, and administering therapy, while in FIG.11B, the single scanning waveguide is used for 3D imaging, obtaining atissue biopsy, and monitoring endoscopic surgery. While in both theseFigures, many of the components are identically provided, it is helpfulto recognize that by making small modifications to the components thatare used as part of the system, different functionality can be provided.In a system 460 shown in FIG. 11A, an interactive computer workstationmonitor 462 enables medical practitioners to control the scanningoptical fiber and to execute software algorithms used for imaging,diagnosis (e.g., optical biopsy), and administering therapy. A highresolution color monitor 464 receives signals from a scanning opticalfiber 484 that are conveyed over an optical fiber system 488 to adistribution console 472. Optional RGB detectors may be provided if notincluded internally within the patient's body adjacent to scanningoptical fiber 484. An ROI 486 is scanned by the optical fiber to producethe high resolution color images displayed to a user. In an exemplarypassive display embodiment, two cathode ray tube monitors (CRTs) displayimages using two different contrast modes to generate the images of thesame object (e.g., tissue). For example, the same resonant drivenscanning optical fiber may produce both a full-color optical image onone CRT and a grayscale fluorescence image on the other CRT monitor. Ifthe optical properties of the excitation and signal do not overlap, thentwo or more images may be generated simultaneously. Otherwise, the twoimages are either captured in a frame sequential method or inalternating line sweeps of the fast resonant scanner. To switch betweenimage contrast modes (full-color optical and fluorescence), the lightsources are shuttered or directly turned off/on. Synchronized in timeduring the modulation of both illumination power and spectral range, thesignals from the photon detectors are recorded and displayed as separateimages. In this example, having a second fluorescence image of the sameROI, a medical practitioner can find and positively identify small orpre-cancerous lesions that may or may not be visible on a standardwhite-light image.

It is contemplated that one of the two displays might be interactive,such as by using a touch screen monitor or interactive foot mouse orpedal that enables the medical practitioner to select (draw the outlineof) an ROI for laser surgery. Since the image may be moving, the touchscreen monitor will require the image to be captured and frozen in time.However, once this ROI is outlined, image segmentation and objectrecognition algorithms may be implemented to keep the ROI highlightedduring real-time image acquisition and display. The interactive monitorcan provide sidebar menus for the practitioner to set parameters for thelaser therapies, such as power level and duration of laser radiationexposure. The second display would not be used interactively, but ispreferably a high resolution monitor displaying the real-time opticalimage in full-color or grayscale. If IR photon detectors are integratedinto the endoscope, the high resolution display with pseudo-color willallow the practitioner to monitor the progress of laser therapies, suchas tissue heating and/or tissue irradiation in laser surgery.

The scanning optical fiber within the capsule is positioned at a desiredlocation within the patient's body, opposite ROI 486, using the tetherand an optional manual controller that facilitates tip navigation andstabilization, as indicated in a block 466. The disposition of thecapsule within the lumen can be automatically determined based upon aposition sensor signal or simply by monitoring the distance that thetether extends into the lumen, with reference to a scale provided on thetether, as discussed below in connection with FIG. 13. Within ROI 486,optical biopsy “spots” 485 illustrate the spatial and temporaldistribution of single-point spectral measurements to diagnose fordisease. These spots are distributed much like the current practice ofinvasively taking tissue samples for in vitro biopsy analysis. Each spotmay be analyzed spectroscopically during a frame cycle of the opticalscanner, separating t₁ and t₂ by, for example, about 1/30 second. Inaddition to the image provided by the scanning optical fiber, IR thermalphotodetectors (and an optional temperature monitor) as indicated in ablock 468 could be included for receiving IR signals from the ROI.

To facilitate control of the motion of the scanning optical fiber orlight waveguide, electrical power for microsensors and controlelectronics are provided, as indicated in a block 470. The signalsprovided by the control electronics enable amplitude and displacementcontrol of the optical fiber when the actuator that causes it to scan iscontrolled by both electrical hardware and software within block 470. Aspectrophotometer and/or spectrum analyzer 474 is included fordiagnostic purposes, since the spectral composition of light receivedfrom ROI 486 and distribution of optical biopsy spots 485 can be usedfor screening and diagnosis for such diseases as cancer by a medicalpractitioner evaluating the condition of the ROI in the lumen, basedupon spectral photometric analysis. To illuminate the ROI so that it canbe imaged, red, green, and blue light sources 476, 478, and 480 arecombined and the light that they produce is conveyed through the opticalfiber system to scanning optical fiber 484 within the capsule. The lightsource used for spectral analysis may be a high power pulse from one ofthe external RGB light sources (e.g., lasers), or a secondary laser orwhite light source. Since signal strength, time, and illuminationintensity are limiting, a repeated single-point spectroscopic methodwill be initially employed, using flash illumination. In addition, thesame or a different high power laser source 482 can be employed toadminister therapy, such as PDT, the laser ablation of dysplasia,neoplasia, and tumors, and other types of therapy rendered with a highintensity source.

In using system 460, a medical practitioner navigates and maneuvers theflexible tether and attached capsule that includes the scanner, to anappropriate region of the lumen in a patient's body while watching thehigh resolution color monitor displaying the standard, full-colorendoscopic image. The search for tumors, neoplasia, and/or pre-cancerouslesions in the lumen can begin by simply watching the monitor. A secondmonitor (not separately shown) included with spectrophotometer andspectrum analyzer 474 displays a fluorescence mapping in pseudo-colorover a grayscale version of the image produced by the scanner in thecapsule. When abnormal appearing tissue is found, the capsule isoptionally mechanically stabilized (e.g., by inflating an attachedballoon, as explained below). The ROI on the lumen wall is centeredwithin the FOV of the scanner, then magnified using a multi-resolutioncapability provided by the scanner. The size of the ROI or cancer isestimated and a pixel boundary is determined by image processing eitherthe visible image or the fluorescence image. If spectroscopic diagnosisis required, such as LIFS, the distribution of optical biopsy points isestimated along with illumination levels. The diagnostic measurementsare performed by automatically delivering the illumination repeatedlyover many imaging frames. The user can cease the diagnosis or have theworkstation continue to improve signal-to-noise ratio and/or density ofsampling until a clear diagnosis can be made from the images produced ofthe lumen inner surface by the scanner in the capsule. The results ofdiagnosis is expected to be in real-time and overlaid on top of thestandard image.

If optical therapy is warranted, such as PDT, then an optical radiationexposure is determined and programmed into the interactive computerworkstation controlling the scanner system in the capsule. The PDTtreatment is an optical scan of high intensity laser illuminationtypically by high power laser source 482, pre-selected for the PDTfluorescent dye, and is controlled using dichroic filters, attenuators,and electromechanical shutters, as explained above. In aframe-sequential manner, both fluorescence images and visible images areacquired during PDT treatment rendered using the scanner in the capsule.The medical practitioner monitors the progress of the PDT treatment byobserving these images acquired with the scanner, on both displays.

With reference to FIG. 11B, a scanning system 460′ provided in a capsuleis used for 3D imaging, biopsy, and monitoring endoscopic surgery of aninner surface of a lumen. To enable 3D imaging in a pseudo-stereo viewof the ROI, an HMD 490 is included. In addition, the system includeshigh resolution color monitor 464, which was described above inconnection with FIG. 11A. Also, an IR optical phase detector 492 isincluded for range finding within the lumen. High frequency modulationof IR illumination can be measured to determine phase shifts due tooptical propagation distances on the order of a few millimeters. Thedistance between the distal end of the scanning optical fiber or lightwaveguide in the capsule and ROI 486 can be important in evaluating theintensity of light that should be applied during endoscopic surgery, formapping a specific ROI 487 to determine its boundary or size, and fordetermining the size and shape of features such as the area of dysplasiaor volume of a tumor comprising the ROI in the lumen. An UV-visiblebiopsy light source 494 enables an optical biopsy to be carried out atspecific ROI 487. The spectrophotometer and spectrum analyzer in block474 are useful in monitoring the status of the ROI during the endoscopicsurgery being carried out, since the condition of the ROI during theendoscopic surgery can sometimes best be determined based upon thespectrum analysis provided by this instrumentation. In other respects,the components used for the alternative functions provided in FIG. 11Bare identical to those in FIG. 11A.

When using system 460′, a medical practitioner again searches forneoplasia by moving the tether and capsule to reposition the scannerwhile watching high resolution color monitor 464, which shows thevisible wavelength (full-color) image. When an ROI is found, the capsulecan be mechanically stabilized, e.g., by inflating a balloon attached toit, as discussed below. Again, the ROI is centered within the FOV, andthen magnified with the multi-resolution capability. However, if thesurrounding tissue is moving so the acquired image is not stationary, asnapshot of the image is captured and transferred to the interactivecomputer workstation monitor, which is preferably an interactivedisplay. The boundary of the stationary ROI is outlined on theinteractive display screen, and an area of dysplasia or volume of thetumor is estimated from a diameter measurement in pixels and a distancemeasurement between the scanner and the tissue using IR optical phasedetector 492 for range finding. An optical biopsy is taken withUV-visible biopsy light source 494, which can be an opticalfiber-coupled arc lamp for elastic scattering spectroscopy (ESS). Ifwarranted for this cancerous or pre-cancerous tissue, the opticalradiation exposure is calculated, and a treatment protocol is programmedinto interactive computer workstation monitor 462. Digital imageprocessing algorithms can be calibrated for automatically segmenting theROI or processing the scanner signal to eliminate motion artifacts fromthe acquired images in real-time, which may be equivalent or less thanthe display frame rate. The laser surgical treatment and/orcauterization can occur with high intensity laser 482 (IR) that isoptically coupled with the visible optical scanner. If the IR rangefinding option is not required, but an IR temperature monitor or lasermonitor is desired, then the IR source can instead be used for thesealternative monitoring functions. In a frame-sequential manner, both theIR and visible images are acquired during the laser surgery and/orcauterization. The IR image is either a mapping of the back scatter fromthe laser illumination as it scans the ROI in the lumen, or a thermalimage of the ROI, which can be displayed on the interactive computerdisplay as pseudo-color over a grayscale visible image. The medicalpractitioner monitors the progress of the IR radiation treatment byobserving these acquired images on both the high resolution andinteractive display monitors.

Determining Disposition of Capsule in Body Lumen

An earlier exemplary embodiment of the scanning flexible endoscopeemployed a wheel that rotated with the axial movement of the tether asthe tether was manipulated to control the position of the capsule withinthe esophagus of a patient. However, the use of a contact sensor of thattype may be inaccurate if the presence of saliva, mucous or other bodilyfluids causes the tether to slip on the rotating sensor wheel, so thatthe position of the capsule within the esophagus is not accuratelyreported. In addition, the requirement that friction be maintainedbetween the tether and the rotating sensor wheel may interfere with the“feel” that medical personnel may want to experience when controllingthe capsule with the tether. Accordingly, FIGS. 12 and 13 illustrate twoalternative exemplary embodiments of non-contact sensors for measuringthe relative disposition of the capsule within a body lumen such as theesophagus.

In FIG. 12, the proximal end of a tether 630 is illustrated, external tothe mouth of a patient 636. It will be understood that although notshown in this Figure (or in FIG. 13), the distal end of tether 630extends down into the esophagus of patient 636. Optical indicia 634 areaxially disposed along at least a portion of tether 630 and dependingupon the form of the indicia, can provide either an analog or a digitalindication of the relative disposition of the tether, and thus, of thecapsule, within the esophagus of patient 636. A representation of anexemplary analog optical pattern 680 is illustrated in FIG. 20A, whileFIG. 20B illustrates a representation of an exemplary digital opticalpattern 682.

Those of ordinary skill in the art will understand that many opticalsensors are readily available to read either analog or digital encodeddata provided on the indicia on the tether. For example, a light source(not separately shown) on an optical sensor 638 can be directed towardindicia 634. Alternatively, ambient light can be used to illuminate theindicia. Light reflected or scattered by the indicia on tether 630 isthen received by optical sensor 638, which may include a photodiode orother appropriate photodetector—not separately shown in this Figure.Also, one or more lenses can be included in the optical sensor to focusthe light source (if used) on the indicia and/or the received light onthe photodetector. It is also contemplated that the light source maydirect light through the indicia so that the transmitted light isreceived by a photodetector on the opposite side of the indicia from thelight source. However, since that approach is less likely to beimplemented because of issues related to transmission of light throughthe periphery of a tether, it is not shown in the drawings.

The optical sensor can employ ultraviolet, visible, or infrared lightfrom a light emitting diode (or other appropriate light source) and canuse an optical fiber (not shown) to convey the light from such a sourcetoward the indicia on the tether. Similarly, another optical fiber (notshown) can be used to collect the light from the indicia and convey ittoward the photodetector. Use of shorter wavelength light and highernumerical aperture lenses for the collection optical fiber can improvethe spatial resolution with which the indicia are read on the tether.The indicia can be applied axially around the entire circumference of atleast a portion of the tether, so that the indicia can be read by theoptical detector regardless of the rotational orientation of the tetherabout its longitudinal axis.

In FIG. 13, the indicia on tether 630 comprise a magnetic media 642, forexample, a magnetic paint or tape, that is applied along thelongitudinal axis of the tether for at least a portion of its length.The magnetic media can store a varying magnetic field that representseither analog or digital data indicating a relative position of thetether and thus, the capsule within a body lumen such as the esophagus,when the data are detected or read by a magnetic sensor 640. Magneticsensor 640 can include a sensitive magnetic pickup coil (not separatelyshown) like those used in tape recorder heads. The magnetic media canencode the position data as analog or digital data, using varyingmagnetic intensity, modulation, frequency, or a combination of thesetypes of encodings. It is also contemplated that the magnetic encodingcan be read by the magnetic sensor, and its signal can be used toindicate both a relative position of the capsule in a visual display aswell as providing an audible pitch that changes to indicate the relativeposition of the capsule in the body lumen.

The relative position of the tether and the capsule in a body lumen canbe important for several reasons. First, the medical practitioner canrelate the condition of the internal surface of body lumen that isevident in the images being produced by the image scanner included inthe capsule with the position of the capsule in the body lumen, so thata condition such as BE as a specific location in the body lumen isclearly known. With this information, the same location in the bodylumen can subsequently be accessed for further diagnostic procedures orto render a therapy. FIG. 14 illustrates how a non-contact positionsensor 646 (such as the optical or magnetic sensors of FIGS. 12 and 13)reads the indicia on tether 652 to produce a position signal that isinput to a processor in SFE base station 394. A position determinationfunction 648 is implemented by the processor to determine at least arelative position of a capsule 650 within the body lumen at any giventime. At the same time, the capsule is producing an image signal withits image scanning device that is input to an image creation function662 carried out by the processor in the SFE base station. Not only doesthe relative position of the capsule enable indexing with the positionof a current image produced by the scanning device in the capsule, itcan also be used for assisting the processor in the SFE base station tomore efficiently stitch together successive axial images to implement astitched mosaic image creation function 664. While these successiveaxial images can be stitched together without the relative position dataprovided by non-contact position sensor 646, it can reduce theprocessing time required to determine where the longitudinal axial edgesof successive images should be joined in the stitching process to createthe axially continuous mosaic image that shows the internal surface of abody lumen along a substantial portion of its length.

The data provided by position determination function 648 can indicatethe actual distance that the capsule has moved from a reference positionto any subsequent position. For example, if a reference position for thecapsule corresponding to its disposition at the gastroesophagealjunction is determined from images produced by the capsule, subsequentmotion of the capsule up the esophagus can be expressed as an actualdistance from that reference position using the signal produced bynon-contact position sensor 646. Thus, once this reference position isdetermined, the distance from the reference position to a region on theinternal surface of the esophagus where apparent BE conditions areobserved in the images can be determined from the position data. Thisregion can then be readily found again by repeating the step ofestablishing the reference and advancing the capsule upwardly the samedistance noted previously.

Optionally, it may be desirable to gently clean bodily fluids such assaliva and mucous from tether 652 as it is pulled from the body lumen oresophagus, before the bodily fluids on the tether reach non-contactposition sensor 646. As illustrated in FIG. 15, an elastomeric cone 670or other type of scraper fitted over tether 652 can wipe bodily fluids672 from the tether outer surface without applying any significantfriction to the tether that would interfere with the medicalpractitioner feeling its motion through the body lumen. The bodilyfluids can simply drip onto an absorbent material or sponge (not shown)or can be collected in a small tray (also not shown) as drips 674 fallaway from the peripheral lower edge of the elastomeric cone.

Use of a Balloon Coupled to Capsule

FIG. 16 illustrates a capsule 570 that has an inflatable balloon 574coupled to its proximal end. The balloon does not interfere withilluminating light 572 being directed from the distal end of the capsuleto an inner surface 582 of the lumen in which the capsule is disposed. Avolume 586 within balloon 574 is selectively inflated with fluid or airthat is conveyed through a lumen 578 within a tether 576. The fluidexits lumen 578 through at least one opening 588 that is formed in theportion of the tether encompassed by the balloon.

The balloon can be inflated to serve one or more distinct purposes, asfollows. For example, balloon 574 can be inflated so that peristalticmuscle tissue action advances the balloon and the capsule through thelumen; the larger diameter of the balloon enables the force applied bythe muscle tissue to more efficiently advance the balloon and theconnected capsule through the lumen. As a further option, the balloon,when inflated, can convey a pressure from a wall of a lumen in which theballoon is disposed, to a pressure sensor (not shown here—but discussedabove) that is on the capsule or otherwise in fluid communication withinterior volume 586, so that the pressure exerted by the lumen wall canbe monitored externally of the lumen. The pressure can be determinativeof various conditions or provide other information of interest to aclinician.

Instead of enabling the capsule to advance, the balloon can be at leastpartially inflated to enlarge a cross-sectional size of the balloon,thereby preventing further movement of the capsule through a portion ofa lumen or other passage having a cross-sectional size that is smallerthan that of the balloon. Finally, the balloon can be inflated togenerally center and stabilize the capsule within a lumen of thepatient's body so that scanning of the inner surface of the lumen toproduce images can be more effectively carried out.

Electrical Contacts to Stimulate Peristalsis

A capsule 590 is shown within a lumen 592 in FIG. 17 and includes aplurality of electrical contacts 594 disposed on the outer surface ofthe housing of the capsule. Electrical contacts 594 are connected toleads 598, which extend within a passage 602 formed in a tether 600. Theleads are coupled to an electrical power source (not shown). Anelectrical voltage is thereby selectively applied to electrical contacts594 through leads 598, thereby contacting muscle tissue 604 andstimulating peristalsis in the muscle tissue of lumen 592, whichadvances the capsule through the lumen. Optionally, electrical contacts596 that are connected to tether 600 proximal of capsule 590 can beemployed in lieu of or in addition to electrical contacts 594 tostimulate peristalsis of the muscle tissue.

Mechanical Biopsy

FIG. 18 illustrates a capsule 620 that is coupled to a tether 624.Tether 624 includes an annular passage 622 within which one or morecytological brushes 626 or biopsy forceps (not shown) are controllablyadvanced to contact the inner surface of the lumen in which capsule 620is disposed. Cytological brush 626 is advanced from annular passage 622into contact with the tissue on the inner surface, so that cells of thetissue lining the lumen are transferred onto the bristles of the brush.The cytological brush is then withdrawn into the annular passage andafter the capsule and tether are withdrawn from the lumen in thepatient's body, the cell sample can be removed from the bristles forfurther processing and study. Although not shown, the annular passagecan be used to pull back a flap on the capsule that exposes bristlesthat can be advanced from the capsule. Instead of an annular passage,the cytological brush, a fine needle, or other type of mechanical biopsydevice can be advanced through a piggyback passage provided on thetether (not shown). A grasping device may also be employed in theannular or piggyback passage to gather a sample from the lumen andretract with the sample back into the passage. Such a passage can alsobe used as an intake for a fluid that is drawn through the passage tothe proximal end of the tether that is outside the patient's body.

Multiple Images

As noted above, it is contemplated that a plurality of scanners can beincluded in the capsule, in accord with the present invention. Sinceeach of the scanners are relatively small in size, they can beconfigured in a spaced-apart array that can image a large field of view,encompassing, for example, an entire 360° view of the inner surface of alumen. Alternatively, as shown in FIG. 19, a single scanner can be usedin a capsule 650, to image the four sides of a lumen 672 (including, thetwo sides shown, as well as the side behind the pyramidal mirror and theside opposite, neither of which is visible in this Figure). Capsule 650is connected to a tether 652 that extends externally of lumen 672. Amoving optical fiber 654 in the capsule emits light that is directedthrough a lens 656, toward a pyramidal-shaped mirror 658. The adjacentmirror surfaces of pyramidal mirror 658 reflect the light from lens 656in the four different directions and through lenses 660 a and 660 b (theother two lenses not being shown). Light reflected from the innersurface of lumen 672 is detected by annular detectors 670 a and 670 b(the other two annular detectors not being shown). If the extent ofoverlap of the images provided on the four sides of capsule 650 isincomplete, a user can rotate tether 652, as indicated by an arrow 674,which will rotate capsule 650 to change the direction in which thescanning of the inner surface occurs, so that additional images can beproduced and optionally connected together to form a full panoramic viewof the inner surface of the lumen.

Multiple Tether/Capsule Position Sensors

To increase the precision and accuracy with which the relative positionof the tether/capsule is measured, two optical or magnetic sensors canbe used concurrently to read the indicia on the tether. Interpolationbetween the optical or magnetic scaling provided by the indicia can alsobe employed. The spacing of these two or more sensors will be preciselydetermined, and one sensor can be employed for measuring a full-step,while the other sensor is measuring a half-step. FIG. 21 illustrates anexemplary embodiment of a dual color encoding pattern 800 with dualsensors. To detect red analog or digital markings 818 on a tether 820, ared laser 802 produces red wavelength light that is directed either infree space, or as shown in this exemplary embodiment, through an opticalfiber 822 toward a lens 806, which focuses the red light onto dual colorencoding pattern 818. Red light reflected from the red portion of thedual color encoding pattern passes through a lens 808 and is conveyedeither through free space, or as shown, through an optical fiber 824, toa red wavelength light photodetector 804. Similarly, on an opposite sideof tether 820, a green laser produces light having a green wavelengththat is conveyed in free space or through an optical fiber 826 toward alens 814, which focuses the light onto dual color encoding pattern 818.Green light reflected from the green portion of the dual color encodingpattern passes through a lens 816 and through free space or as shown,through an optical fiber 828, which conveys the green light to a greenlight photodetector 812. Appropriate red and green bandpass filters (notshown) will likely be included in the respective red and green lightphotodetectors to limit the wavelength of the light reaching thephotodetector photodiode. The red and green light photodetectors eachproduce position signals that are processed to effectively double theresolution with which the relative position of tether 820 and thecapsule to which it is coupled is determined by the processor in the SFEbase station. It would be desirable to be able to determine the relativeposition of the capsule in a body lumen such as the esophagus with aresolution of at least 1.0 mm. Instead of red and green light encodingand detection, other combinations of colored light can be used. Forexample, red and infrared light sources and photodetectors may be used,since the wavelengths of red and infrared light are within the peaksensitivity waveband (700-900 nm) of silicon photodiodes (which can beemployed as the two different color photodetectors).

As another option, actual high-resolution scaling can be printed inoptical contrast lettering on the tether, and the non-contact sensor caninclude an optical character reader that enables the processor in theSFE base unit to “read” the scaling at high spatial resolution. Further,the clinician can also visually directly read the scales on the tether,as well, during use of the tether for positioning the capsule in thebody lumen.

FIGS. 22A and 22B illustrate details of a tether 830, which includes asupporting structure 832 around a central region 838 within which aredisposed optical fibers, conductive wires, lumens, etc. On the outersurface of supporting structure 832 is a data layer 834 (i.e., theapplied tape or markings that convey analog or digital positioninformation). Finally a protective coating that is biocompatible andprevents abrasion or damage to the data layer overlies the data layer.The protective coating can comprise a clear polymer or other suitableclear, biocompatible material.

For use in screening for BE in the esophagus, a clinician will generallywant to initially employ the scanning capability of the capsule forimaging the region immediately above and adjacent to thegastroesophageal junction where the esophagus is joined to the stomach.The average distance from the mouth of a patient down the esophagus to aposition of the capsule suitable for scanning to produce images of thisregion is about 39 cm. To facilitate the initial positioning of thecapsule, as shown in FIG. 23, tether 652 can be provided with a visibleindication, such as a red mark 840 that is located about 39 cm abovecapsule 650. Thus, when the clinician observes that red mark 840 isdisposed at about the lips of the patient, it will be evident that forthe average patient, capsule 650 has been carried down the esophagus tothe point immediately above the gastroesophageal junction. The cliniciancan confirm this position of the capsule by viewing the images of theregion adjacent to the capsule at that point. Small adjustments can bemade to the position of the capsule, as necessary, and additionaldifferently colored visible marks 842 and 844 are provided on each sideof red mark 840 to assist the clinician in keeping track of the smalladjustments. Of course, the position signal produced by monitoring thedata provided on the tether with the non-contact position sensor canalso be employed for making small adjustments. Once the initial positionrelated to the gastroesophageal junction has been determined, thatposition can then serve as a reference position in regard to therelative position determined from the position data on the tether.

FIGS. 24-26 illustrate three different exemplary embodiments thatillustrate slightly different approaches for supplying a pulse of afluid (typically, a pulse of air) to a position adjacent to the distalend of the tether or of the capsule. The pulse of fluid such as air canbe employed to assist in more readily moving the capsule within theesophagus (or other body lumen) and in particular, in moving the capsulethrough the LES between the esophagus and the stomach. To facilitatefree movement of the capsule within the esophagus and through the LES,an air pulse is supplied down a lumen within a tether 850 from a sourceof pressurized air (and a valve to provide the air pulse) via a tube856. The lumen continues through the capsule and opens to the body lumenat an orifice 854 that is formed in the housing of a capsule 858. Thisbolus or air pulse is thus selectively delivered to the interior of theesophagus (or other body lumen) at a point adjacent to the capsule,causing the wall of the esophagus to be distended and the LES at the topof the stomach to autonomously open.

Another exemplary embodiment for delivering the air pulse shown in FIG.25 includes a piggy-back tube that is attached along an external surfaceof tether 860 and has a distal port 864 disposed adjacent to the distalend of the tether, so that the air pulse is released into the esophagusadjacent to a capsule 866. Both exemplary embodiments shown in FIGS. 24and 25 provide directional pulses of air, which can be used to forcenon-axially symmetric actions and reactions to the pneumatic pressure.The resultant motion of the capsule and reaction of the tissue can becontrolled for maneuvering and positioning the capsule with respect tothe lumen wall. In contrast, FIG. 26 illustrates an exemplary embodimentthat uses a tether 870 as a guide wire for a larger tube 872 that exertsaxially symmetric pressure from the fluid pulse. Tube 872 has an annularopening 876 disposed at its proximal end for receiving a pulse ofpressurized air from a source and valve (neither shown) and anotherannular opening 874 at its distal end, which is adjacent to the distalend of the tether and to capsule 866, so that the pulse of air causesthe LES to open and/or the internal wall of the esophagus or other bodylumen in which the capsule is disposed to autonomously distendoutwardly. Other techniques for delivering a pulse of air or other typeof fluid can also be used for this purpose.

Although the concepts disclosed herein have been described in connectionwith the preferred form of practicing them and modifications thereto,those of ordinary skill in the art will understand that many othermodifications can be made thereto within the scope of the claims thatfollow. Accordingly, it is not intended that the scope of these conceptsin any way be limited by the above description, but instead bedetermined entirely by reference to the claims that follow.

The invention in which an exclusive right is claimed is defined by thefollowing:
 1. A method for imaging a body lumen of a patient, the methodcomprising: providing an imaging apparatus comprising a scanning capsulecoupled to a flexible tether, the scanning capsule comprising a scanningdevice disposed within a capsule housing; introducing the scanningcapsule and at least a portion of the flexible tether into the bodylumen of the patient by swallowing, wherein the scanning capsuleadvances along the body lumen with normal peristalsis; scanning lightonto a portion of the body lumen using the scanning device; detectinglight from the portion of the body lumen using a light sensor;generating one or more images of the portion of the body lumen inresponse to the detected light; determining a rate for withdrawing thescanning capsule from the body lumen based on the one or more images;and withdrawing the scanning capsule from the body lumen according tothe determined rate.
 2. The method of claim 1, further comprisingstitching the one or more images together so as to generate a panoramicimage of the portion of the body lumen.
 3. The method of claim 2,wherein the stitching is performed using automated image stitchingsoftware.
 4. The method of claim 2, further comprising determining alocation of the scanning capsule relative to the body lumen based on thepanoramic image.
 5. The method of claim 1, wherein the rate isdetermined based on one or more of quality or content of the one or moreimages.
 6. The method of claim 1, wherein the determining andwithdrawing steps are performed using an automated computer system. 7.The method of claim 1, wherein the light scanned onto the portion of thebody lumen comprises a fluorescence excitation wavelength.
 8. The methodof claim 7, wherein the detected light comprises both light reflectedfrom the portion of the body lumen and light emitted from the portion ofthe body lumen in response to the fluorescence excitation wavelength. 9.The method of claim 7, wherein the fluorescence excitation wavelength isconfigured for photodynamic therapy.
 10. The method of claim 1, furthercomprising selectively transmitting a pulse of fluid into the body lumenthrough a fluid lumen coupled to the flexible tether, the fluid lumencomprising a proximal end coupled to a source of pressurized fluid and adistal opening positioned in or near the scanning capsule.
 11. A systemfor imaging a body lumen of a patient, the system comprising: an imagingapparatus comprising a scanning capsule coupled to a flexible tether,the scanning capsule comprising a scanning device disposed within acapsule housing, wherein the scanning capsule is sized to be introducedinto the body lumen of the patient by swallowing and advanced along thebody lumen with normal peristalsis; a reel coupled to the flexibletether; and one or more processors configured to: scan light onto aportion of the body lumen using the scanning device, detect light fromthe portion of the body lumen using a light sensor, generate one or moreimages of the portion of the body lumen in response to the detectedlight, determine a rate for withdrawing the scanning capsule from thebody lumen based on the one or more images, and withdraw the scanningcapsule from the body lumen using the reel according to the determinedrate.
 12. The system of claim 11, wherein the one or more processors arefurther configured to stitch the one or more images together so as togenerate a panoramic image of the portion of the body lumen.
 13. Thesystem of claim 12, wherein the one or more processors are furtherconfigured to determine a location of the scanning capsule relative tothe body lumen based on the panoramic image.
 14. The system of claim 13,further comprising a display operably coupled to the one or moreprocessors and configured to display the location of the scanningcapsule relative to the body lumen.
 15. The system of claim 11, whereinthe rate is determined based on one or more of quality or content of theone or more images.
 16. The system of claim 11, wherein the lightscanned onto the portion of the body lumen comprises a fluorescenceexcitation wavelength.
 17. The system of claim 16, wherein the detectedlight comprises both light reflected from the portion of the body lumenand light emitted from the portion of the body lumen in response to thefluorescence excitation wavelength.
 18. The system of claim 16, whereinthe fluorescence excitation wavelength is configured for photodynamictherapy.
 19. The system of claim 11, wherein the scanning devicecomprises an optical fiber configured to be driven in a scanningpattern.
 20. The system of claim 11, further comprising: a source ofpressurized fluid; and a fluid lumen coupled to the flexible tether andcomprising a proximal end coupled to the source of pressurized fluid anda distal opening positioned in or near the scanning capsule.